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Published on: August 8, 2022
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Natural history and outcomes in paediatric RASopathy-associated hypertrophic cardiomyopathy
Olga Boleti1,2, Gabrielle Norrish1,2, Ella Field1,2
1Centre for Inherited Cardiovascular Diseases, Department of Cardiology, Great Ormond Street Hospital, London, UK.
ESC Heart Failure
|January 13, 2024
Summary
Children with RASopathy syndromes and hypertrophic cardiomyopathy (HCM) have a distinct survival rate that varies by syndrome. Congestive cardiac failure and non-sustained ventricular tachycardia predict mortality in these pediatric patients.
Area of Science:
- Pediatric Cardiology
- Genetics
- Cardiovascular Research
Background:
- RASopathy syndromes are genetic disorders associated with various clinical features, including cardiac abnormalities.
- Hypertrophic cardiomyopathy (HCM) is a common cardiac manifestation in children with RASopathies, impacting their long-term health.
- Understanding the natural history and mortality predictors in this specific population is crucial for clinical management.
Purpose of the Study:
- To describe the natural history of RASopathy-related HCM in children.
- To identify predictors of all-cause mortality and sudden cardiac death (SCD) or equivalent events.
- To compare outcomes across different RASopathy syndromes.
Main Methods:
- Retrospective cohort study involving 14 pediatric cardiology centers in the UK and Ireland.
- Included children under 18 years with HCM and a RASopathy diagnosis (Noonan syndrome, NSML, Costello, CFCS, NS-LAH).
- Analyzed survival data and identified mortality predictors using univariate analysis.
Main Results:
- 149 patients were recruited; Noonan syndrome was most common (74.5%).
- Over a median follow-up of 197.5 months, 15.43% of patients died.
- Survival varied by RASopathy syndrome, with Noonan-like syndrome showing worse survival despite a milder HCM phenotype.
- Congestive cardiac failure (CCF), non-sustained ventricular tachycardia (NSVT), and LVOT gradient were significant predictors of mortality or SCD/equivalent events.
Conclusions:
- RASopathy-related HCM represents a unique patient group with variable prognoses.
- Noonan-like syndrome patients have a distinct phenotype with poorer survival outcomes.
- Identifying predictors like CCF, NSVT, and LVOT gradient aids in risk stratification and management of pediatric patients with RASopathy-related HCM.
